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Activation of EGF receptor by oxidized LDL
Author(s) -
Suc Isabelle,
Meilhac Olivier,
Lajoiemazenc Isabelle,
Vandaele Jean,
Jurgens Günther,
Salvayre Robert,
Nègresalvayre Anne
Publication year - 1998
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.12.9.665
Subject(s) - chemistry , epidermal growth factor receptor , signal transduction , phosphorylation , tyrosine phosphorylation , oxidative stress , lipid peroxidation , receptor , intracellular , tyrosine , microbiology and biotechnology , epidermal growth factor , tyrosine kinase , reactive oxygen species , receptor tyrosine kinase , biochemistry , biology
Oxidized low density lipoproteins (oxLDL) are thought to play a major role in atherosclerosis. OxLDL exhibit a wide variety of biological effects resulting from their ability to interfere with intracellular signaling. The cellular targets and primary signaling events of oxLDL are unknown. We report that oxLDL elicit, in intact cells, tyrosine phosphorylation of the epithelial growth factor receptor (EGFR) and activation of its signaling pathway. This activation triggered by oxLDL was associated with derivatization of reactive amino groups of EGFR and was mimicked by 4‐hydroxynonenal (4‐HNE, a major lipid peroxidation product of oxLDL). Immunopurified EGFR was derivatized and activated in vitro by oxLDL lipid extracts and 4‐HNE, thus indicating that 1 ) EGFR may be a primary target of oxidized lipids and 2 ) EGFR derivatization may be associated with activation. The reported data suggest that EGFR acts as a sensor for oxidized lipids. We therefore propose a novel concept of the mechanism by which oxidized lipids (contained in oxLDL or more generally produced during oxidative stress) are able to activate receptor tyrosine kinase and subsequent signaling pathways, resulting finally in a gain of function.—Suc, Isabelle, Meilhac, Olivier, Lajoie‐MAZENC, Isabelle, Vandaele, Jean, Jurgens, GüNTHER, Salvayre, Robert, NèGRE‐SALVAYRE, Anne Activation of EGF receptor by oxidized LDL. FASEB J. 12, 665–671 (1998)